A study of the mechanism (s) of increased intraocular pressure induced by topical administration of glucocorticoids is proposed. In addition, the effect of cortisol on certain lens enzyme systems will be studied in order to determine a possible mechanism for cataract formation associated with the pharmacological use of glucocorticoids. The biological efficacy of the hormone depends largely on its uptake and metabolism within the target tissue. It is planned therefore to determine the activity of enzymes regulating the metabolism of cortisol in ocular tissues, study the interaction of enzyme inducers on this system and measure the in vivo and in vitro uptake and intracellular binding of labelled corticosteroids in the eye. Both animal and human eyes will be used. This investigation uses an animal model for cortisol-induced glaucoma. Enzyme assays will be carried out by incubating ocular tissues in a mixture containing the appropriate labelled steroid substrate and coenzyme. The radiometabolites will be identified by a thin layer chromatography system and by crystallization to constant specific activity. The pattern of cortisol metabolism and enzyme activities will be correlated with steroid induced changes of intraocular pressure. The effect of medroxyprogesterone acetate (inducer of steroid A-ring rductase) and phenobarbital (inducer of hydroxylases) will be studied. This proposed research will help clarify the metabolism of steroids in ocular tissues and may provide insight to an understanding of cortisol-induced glaucoma and cataract.